Horm Metab Res 2021; 53(08): 562-569
DOI: 10.1055/a-1480-7519
Endocrine Research

miRNA-483–5p Targets HDCA4 to Regulate Renal Tubular Damage in Diabetic Nephropathy

Lu Liu
1  Department of Endocrinology, Seventh People’s Hospital of Shanghai University of TCM, 200137, Shanghai, China
,
Huanzhen Chen
2  Department of Endocrinology, Putuo People’s Hospital, Tongji University, Shanghai, 200060, China
,
Jie Yun
3  Department of Nephrology, Heilongjiang University of Chinese Medicine, Heilongjiang, China
,
Liqun Song
3  Department of Nephrology, Heilongjiang University of Chinese Medicine, Heilongjiang, China
,
Xiaopeng Ma
3  Department of Nephrology, Heilongjiang University of Chinese Medicine, Heilongjiang, China
,
Shan Luo
3  Department of Nephrology, Heilongjiang University of Chinese Medicine, Heilongjiang, China
,
Yexu Song
4  Department of Science and Technology, Heilongjiang University of Chinese Medicine, Heilongjiang, China
› Author Affiliations
Funding Information This study was funded by the National Natural Science Foundation of China (Grant number 81804088); Construction Program of National TCM Clinical Research Base (Grant number JDZX2015192); University Nursing Program for Young Scholars with Creative Talents in Heilongjiang Province (Grant number UPYSCT-2018222); Heilongjiang Postdoctoral Fund (Grant number LBH-Z15210); Natural Science Foundation of Heilongjiang Province of China (Grant numberH2016078); and Research Foundation of Heilongjiang University of Chinese Medicine (Grant number 2015bs01).

Abstract

This study was designed to evaluate the diagnostic value of miR-483–5p in diabetic nephropathy (DN), and its effect and mechanism on apoptosis and inflammation of human proximal renal tubular cells (HK2) induced by high glucose (HG). Thirty healthy controls, 30 types 2 diabetes mellitus (T2DM) patients, and 28 DN patients were enrolled. miR-483–5p mRNA levels in serum were analyzed by RT-qPCR assays. The receiver operating characteristic curve (ROC) was used to analyze the diagnostic value of miR-483–5p in DN. HK2 cells were induced by HG to establish an in vitro study model. CCK-8 and flow cytometry was used to detect cell viability, apoptosis, and reactive oxygen species (ROS) generation. Inflammation levels were measured by ELISA. Luciferase reporter assay was used to detect target genes of miR-483–5p. miR-483–5p was decreased in DN patients. The decreased level of miR-483–5p was positively correlated with estimated glomerular filtration rate (eGFR) and negatively correlated with proteinuria. miR-483–5p can significantly distinguish DN patients from healthy controls and T2DM and has a high diagnostic value. miR-483–5p decreased in HK2 cells induced by HG, and overexpression of miR-483–5p reversed HG-induced decreased cell activity, increased apoptosis, ROS production, and inflammation. Histone deacetylase 4 (HDCA4) was markedly increased in DN patients and HG-induced HK2 cells. miR-483–5p directly targeted HDCA4, and increasing miR-483–5p inhibited HDCA4 increased in HG-induced HK2. In conclusion, the results indicate that reduction of miR-483–5p has a high diagnostic value in DN, and overexpression of miR-483–5p has a certain protective effect on HK2 cells induced by HG by targeting HDCA4.



Publication History

Received: 01 March 2021

Accepted: 01 April 2021

Publication Date:
14 June 2021 (online)

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